TRIC-A shapes oscillatory Ca(2+) signals by interaction with STIM1/Orai1 complexes

Trimeric intracellular cation (TRIC) channels have been proposed to modulate Ca(2+) release from the endoplasmic reticulum (ER) and determine oscillatory Ca(2+) signals. Here, we report that TRIC-A–mediated amplitude and frequency modulation of ryanodine receptor 2 (RyR2)-mediated Ca(2+) oscillations and inositol 1,4,5-triphosphate receptor (IP(3)R)-induced cytosolic signals is based on attenuating store-operated Ca(2+) entry (SOCE). Further, TRIC-A–dependent delay in ER Ca(2+) store refilling contributes to shaping the pattern of Ca(2+) oscillations. Upon ER Ca(2+) depletion, TRIC-A clusters with stromal interaction molecule 1 (STIM1) and Ca(2+)-release–activated Ca(2+) channel 1 (Orai1) within ER–plasma membrane (PM) junctions and impairs assembly of the STIM1/Orai1 complex, causing a decrease in Orai1-mediated Ca(2+) current and SOCE. Together, our findings demonstrate that TRIC-A is a negative regulator of STIM1/Orai1 function. Thus, aberrant SOCE could contribute to muscle disorders associated with loss of TRIC-A.